In modern automated pipettors or liquid handlers there are several issues to be addressed to precisely and accurately aspirate and dispense the liquid of interest. Apart from the basic pipetting requirements like the use of precise actuators and adequately designed tips, there are also requirements on the use of in-process controls to monitor the success of the pipetting. For example, the instrument must be able to sense the surface of the liquid that is to be aspirated, to prevent the tip to be inserted too deeply into the fluid and adhere and distribute a significant volume to the outer surface of the tip.
Since the 1980s this is done using capacitative techniques that require a conductive pipetting tip or needle, and typically require a minimum amount of liquid mass available.
A relatively new method for liquid surface detection it to use a pressure based system in which a small airflow is induced whose resistance—and thus pressure—increases if the distance between tip en and liquid surface becomes small enough.
Furthermore, many applications require evidence that liquid was indeed aspirated and dispensed properly. This has lead inter alia to the recording of the pressure profile upon aspiration, by which it can be demonstrated that liquid did indeed flow through the tiny tip orifice when the plungers were moved. This technique also allows recognition of the aspiration of air bubbles or the presence of blocking items like blood clots.
The possibility to detect fluid flowing into the tip is used to provide evidence for the correctness of the aspirated volume, which is a strong prerequisite in volume critical applications like in vitro diagnostics, in which, an incorrect volume of patient material might lead to erroneous clinical interpretation of the test result with severe health consequences and liabilities.
The drawback of all discussed techniques is that they all require a typical minimum liquid volume in the order of 10-20 μl, both for surface detection and for pressure detection. With the ongoing trend to use smaller volumes of samples and chemical reagents, the above techniques have reached the limits of their applicability.